Background: The neutrophil-to-lymphocyte ratio (NLR) has been evaluated as a serum marker of inflammation and oncologic prognosis. In renal cell carcinoma (RCC), a higher preoperative NLR is associated with aggressive clinicopathologic features and is an independent predictor of poor survival. This study builds upon our institution’s prior work with the NLR in metastatic RCC and examines a larger validation cohort that includes localized disease. It also compares the predictive power of the NLR to established kidney cancer prognostic scores. Methods: Our kidney cancer database provided patients with clear cell RCC who underwent nephrectomy from January 2001 to June 2017 and had a documented preoperative NLR within 15 days prior to surgery. The optimal threshold of NLR was determined using receiver operating characteristic (ROC) curve and sensitivity-specificity trade-off analysis. Kaplan-Meier curves and logistic regression analysis were performed to assess the significance and independence of preoperative NLR in predicting OS. Finally, the prognostic ability of NLR was compared to current prognostic scores through chi-square analysis of their respective c-indices. Results: The 441 patient cohort was comprised of 361 patients with localized and/or regional disease and 80 patients with distant metastases. NLR values among all participants ranged from 0.4 to 74.0 (median 3.1). ROC analysis defined an optimal preoperative NLR threshold of 3.5. On multivariate analysis, after adjusting for clinicopathologic features and distant metastatic disease, a NLR ≥ 3.5 was found to be a significant and independent predictor of overall survival (HR = 1.41, 95% CI 1.05-1.91 & p value = 0.024). Our data also revealed no statistically significant difference between the c-indices of NLR and the UISS, SSIGN, or Leibovich scores in predicting survival. Conclusions: In our validation cohort of patients with both metastatic and non-metastatic clear cell RCC, our data show that a preoperative NLR ≥ 3.5 is a significant and independent predictor of overall survival in patients undergoing nephrectomy and is comparable to other established prognostic tools in RCC.